A magnetic resonance imaging (MRI) method used in clinical application is a method of imaging a signal of the protons of water by which contrast between the positional information of protons existing in an organism and the surroundings is displayed two-dimensionally in a grayscale picture. The positional information is obtained by using a gradient magnetic field purposely distorting a static magnetic field in NMR and the contrast is determined by a spin density, a relaxation time, a diffusion velocity, a chemical shift, a phase and the like which are obtained as NMR information of the protons of water, lipid and the like. Particularly, the relaxation time varies according to the configuration and the movement between a water molecule containing a spin to be observed and surrounding molecules, so that the relaxation time advantageously reflects the state of a tissue and is used for diagnosis.
An MRI contrast agent in the related-art adds a contrast to between tissues having distribution quantities of water different from each other by varying the relaxation time of water in a biomedical tissue. In other words, the contrast agent is indirectly detected through a change in the relaxation time of the water protons. There are used a T1 relaxation contrast agent containing Gd and Mn and a T2 relaxation contrast agent using iron oxide, and by the interaction between these metal ions and the water protons, vertical and horizontal relaxations are accelerated.
However, these metal ions tend to be toxic, so that the metal ions are chelated by a ligand for reducing the ability of the biomedical tissue to absorb the metal ions. Consequently, the relaxivity possessed by the metal ions decreases and the effect as the contrast agent decreases. Then, there are disclosed a contrast agent utilizing the PRE effect (paramagnet relaxation enhancement effect) by which a metal ion enhances the relaxivity of the contrast agent by being bonded to a macromolecule (see Patent Document 1), a contrast agent having a high relaxivity by hybridizing a nitroxide compound which is an organic radical and a metal ion (see Patent Document 2), and a contrast agent having an average particle diameter of around 26 nm and having cancer cell selectivity which is produced by conjugating iron oxide nano-particles of a superparamagnet with a polymer (see Non-patent Document 1). However, all of these contrast agents contain metal ions, so that there remains a problem that the safety of the contrast agents in an organism is concerned.
Although there is disclosed a contrast agent using a dendrimer using no metal ion at all and having a nitroxyl group which is an organic radical (Patent Document 3), such a contrast agent has a problem that the relaxivity of the contrast agent is low or there is a synthetic problem for obtaining a size of the contrast agent capable of expecting the cancer cell selectivity.    Patent Document 1
U.S. Pat. No. 4,822,594    Patent Document 2
Japanese Translation of PCT International Application No. JP-A-2001-523215    Patent Document 3
Japanese Translation of PCT International Application No. JP-A-2004-524259    Non-Patent Document 1
J. Am. Chem. Soc., ASAP Article 10. 1021/ja072210i (published on web site in Sep. 25, 2007)